Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen (Ag)-specific CD8+ T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this "memory T-cell inflation" phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life...

Purpose: To study age- and intraocular pressure-induced changes in the glial lamina of the murine optic nerve on the ultrastructural level. Methods: Naïve C57bl/6 mice at various ages spanning the time between early adulthood (3 months) and senescence (30 months) were used in this study. In addition, the intraocular pressure (IOP) was increased in a group of young mice by injection of microbeads into the anterior chamber. The unmyelinated segments of the optic nerve containing the glial lamina were prepared for transmission electron microscopy and imaged at high resolution...

In the central nervous system (CNS), senescent astrocytes have been associated with neurodegeneration. Senescent cells secrete a complex mixture of pro-inflammatory factors, which are collectively called Senescence Associated Secretory Phenotype (SASP). The SASP components can vary depending on the cell type, senescence inducer and time. The SASP has been mainly studied in fibroblasts and epithelial cells, but little is known in the context of the CNS. Here, the SASP profile in senescent astrocytes isolated from Wistar newborn rats induced to senescence by oxidative stress or by proteasome inhibition was analyzed...

Uterine leiomyomas (ULM) grow under high oxidative stress due to a hypoxic microenvironment and defects in redox metabolism. AKT is one major pathway activated by reactive oxygen species (ROS) that maintains ULM growth and survival. We previously reported that AKT inactivated by AKT inhibitors can significantly induce cellular senescence in ULM cells. Since some miRNAs are induced by AKT inhibitors in an ROS-dependent manner, we proposed that these miRNAs may modulate AKT function and cellular senescence in ULM...

Ionizing radiation-exposure induces a variety of cellular reactions, such as senescence and apoptosis. Senescence is a permanent arrest state of the cell division, which can be beneficial or detrimental for normal tissue via an inflammatory response and senescence-associated secretion phenotype. Damage to healthy cells and their microenvironment is considered as an important source of early and late complications with an increased risk of morbidity in patients after radiotherapy (RT). In addition, the benefit/risk ratio may depend on the radiation technique/dose used for cancer eradication and the irradiated volume of healthy tissues...

BACKGROUND: Ultraviolet light exposure generates, in human tissues, radical species, which represent the main cause of photo-aging, DNA damage and skin cancer onset. On the other hand, Mediterranean plants, being continuously subjected to high solar radiation levels, are naturally adapted to take on this type of abiotic stress, thanks to the production of antioxidant secondary metabolites. For these reasons, several plant extracts were documented to be excellent antineoplastic drugs. PURPOSE: We investigated the potential antitumor activity of the flower extract obtained by Spartium junceum L...

Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing...

BMI-1 (B-lymphoma Mo-MLV insertion region 1) is a key protein partner in polycomb repressive complex 1 (PRC1) that helps in maintaining the integrity of the complex. It is also a key player in ubiquitination of histone H2A which affects gene expression pattern involved in various cellular processes such as cell proliferation, growth, DNA repair, apoptosis and senescence. In many cancers, Overexpression of BMI1correlates with advanced stages of disease, aggressive clinicopathological behavior, poor prognosis resistance to radiation and chemotherapy...

Nanostructured calcium phosphate (CaP) and magnesium phosphate (MgP) are promising for the application as the nanocarriers in drug delivery. However, the difference between CaP and MgP nanocarriers in drug delivery is rarely investigated. In this work, we comparatively investigated nanostructured CaP, MgP and calcium magnesium phosphate (CMP) for the delivery of SRT1720, which is a silent information regulator (SIRT1) specific activator with pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2 O2 )-induced endothelial senescence...

A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3-FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and sustain tumor growth. Previously we showed that PAX3-FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as demonstrated by increased YAP1 expression and decreased MST activity...

The homeobox gene HLXB9 encodes for the transcription factor HB9, which is essential for pancreatic as well as motor neuronal development. Beside its physiologic expression pattern, aberrant HB9 expression has been observed in several neoplasias. Especially in infant translocation t(7;12) acute myeloid leukemia aberrant HB9 expression is the only known molecular hallmark and assumed to be a key factor in leukemic transformation. However, up to now only poor functional data exist addressing the oncogenic potential of HB9 or its influence on hematopoiesis...

BACKGROUND: Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secretory factors, demonstrated beneficial effects by reducing tissue damage and stimulation of endogenous repair. However, for therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product...

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation...

BACKGROUND/AIMS: High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of efficient drug therapy, plant-based bioactive peptides have been studied as alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty liver in aging conditions, researchers highly commended the genetically engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is a paucity of reports about the anti-steatosis effects of bioactive peptides against fatty liver development under a combined action of high-fat diet exposure and aging process...

Tripterygium glycosides (TGs) are chemotherapeutic drugs and immunosuppressant agents for the treatment of cancer and autoimmune diseases. We have previously reported that TGs induces premature ovarian failure (POF) by inducing cytotoxicity in ovarian granulosa cells (OGCs). Hence, we report that TGs suppress the expression of the Hippo-YAP/TAZ pathway in murine OGCs in vitro and in vivo. We found that the expressions of miR-181b, miR-15a, and miR-30d, were elevated significantly in the POF. Luciferase reporter assays confirmed that miR-15a targets Lats1 through a miR-15a binding site in the Lats1 3'UTR...

The p66Shc adaptor protein regulates apoptosis and senescence during early mammalian development. However, p66Shc expression during mouse preimplantation development is upregulated at the blastocyst stage. Our objective was to determine the biological function of p66Shc during mouse blastocyst development. Here we demonstrate that a reduced p66Shc transcript abundance following its siRNA-mediated knockdown alters the spatiotemporal expression of cell lineage-associated transcription factors in the inner cell mass of the mouse blastocyst...

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers...